Causal role of gut microbiota in intracranial aneurysm: evidence from a Mendelian randomization study.

Abstract

An increasing number of studies suggest that the alteration of gut microbiota may affect the pathogenesis of intracranial aneurysm (IA). However, the exact causal relationship between gut microbiota and IA has not been confirmed. The instrumental variables (IVs) for gut microbiota were obtained from a meta-analysis of a genome-wide association study (GWAS) conducted by the MiBioGen consortium (n = 13,266). The summary of GWAS data for IA was obtained from a large genome-wide meta-analysis involving 23 cohorts. Five Mendelian randomization (MR) methods were used to investigate the causal relationship between gut microbiota and IA (ruptured and unruptured), unruptured intracranial aneurysm only (uIA), and aneurysmal subarachnoid hemorrhage (aSAH) respectively, with inverse variance weighted (IVW) as the main MR method. All MR results were verified through sensitive analyses. Based on the results of the IVW analyses, it was found that five gut microbiota taxa were causally associated with IA (ruptured and unruptured), seven gut microbiota taxa were causally associated with uIA, and six gut microbiota taxa were causally associated with aSAH. Among these taxa, the genus Bilophila was the only one identified to have significant protective effects against IA (ruptured and unruptured), uIA, and aSAH. The sensitivity analysis did not reveal any significant heterogeneity or horizontal pleiotropy among the included IVs. MR analyses identified several gut microbiota taxa that have a causal relationship with IA. Future research should prioritize understanding the mechanisms underlying this causal relationship, as it is expected to contribute to the development of new methods for predicting and treating IA.